A highly efficient extraction protocol for magnetic particles on a digital microfluidic chip

We present a novel, simple and highly efficient protocol for the extraction of magnetic particles out of individual droplets on a digital lab-on-chip in the presence of a spatially fixed magnet with a permanent magnetic field. In this approach, the particles were extracted from the droplet by the interplay of capillary, magnetic and electrowetting forces, thereby avoiding the use of mechanical components that would be needed for removing the magnet when particle resuspension is required. This droplet manipulation allowed the execution of very efficient and fast washing protocols on the digital microfluidic (DMF) platform. To demonstrate the effectiveness of this particle extraction protocol, an IgG immunoassay was implemented on the DMF platform. Our improved protocol reduced the overall assay variability to 3% coefficient of variation (CV) while all incubation and washing steps were automatically performed on-chip. In addition, the suspended magnetic particles allowed the introduction of a very efficient mixing strategy by using the magnetic particles as magnetic stirrers, resulting in an improvement of 90% in detection limit compared to a passive mixing strategy, solely based on diffusion. (C) 2014 Elsevier B.V. All rights reserved.

From Particles to Pillars

Josias Basil Wacker

Metal oxide nanoparticles and their applications (e.g. in nano-electronics, nano-optics or drug delivery) have seen a growing interest in the past decades. Traditional procedures to synthesize, functionalize and integrate nanoparticles in devices mostly happen in mL to L-sized chemical reactors. An upcoming method uses microfluidic chips, on which these operations are done in pL to nL-sized droplets. The miniaturization of the reactor volumes has several advantages, such as reduced waste and very precise metering of reagents, high degree of controllability of reaction parameters, and high reaction speeds due to short diffusion lengths. The first part of this thesis deals with the generation of simple and complex (interleaved) microdroplets in microfluidic chips. Simple droplets are produced in different oils using a microfluidic flow focusing device. A mathematical model is derived from these experiments, which relates the size of the highly uniform droplets to the oil and water flow rates. I then introduce and discuss a procedure to produce complex double droplets in a uniformly hydrophilic microfluidic chip. These droplets are built up of a spherical unit (consisting of fluorocarbon oil) and an elongated or crescent-shaped non-spherical silicone oil droplet which partially engulfs the fluorocarbon moiety. In the second part of this thesis, simple microfluidic droplets (0.4 nL volume each) are continuously generated on-chip from reagents used for the synthesis of fluorescent silica nanoparticles. The fluorescent dye is embedded in the silica network of the nanoparticles via chemical bonds, which reduces dye leakage from the nanoparticles and increases the stability of the dye, as evidenced by a reduced photochemical bleaching compared to a pure dye solution. The size of the nanoparticles (50–350 nm in diameter) can be easily adjusted by controlling the reaction time and the flow rates of the reactant solutions that constitute the microdroplets. The droplet-based continuous synthesis is contrasted with the layer-wise growth of silica nanoparticles in a batch process inside a mL-sized reactor. Droplet-based synthesis enables a faster reaction and allows improved nanoparticle size uniformity when compared to conventional methods. To exemplify droplet-based surface functionalization of nanoparticles, a very important process in nanoparticle engineering, the grafting of titania particles with gold nanoparticles is shown in a microfluidic chip. To this end, porous titania particles are loaded with a reducing agent and then suspended in water and mixed with chlorauric acid in a droplet-by-droplet manner on-chip. The third part treats the assembly of gold-titania nanocomposites and silica nanoparticles inside droplets into micrometer- and submillimeter-sized superstructures. Two different ways of assembling nanoparticles in droplets are presented in this thesis. The first method relies on the convection-driven merging of aqueous colloidal microdroplets. The microdroplets are generated in the bulk and contain about one nanoparticle each. After the complete evaporation of water, spherical superstructures of silica or gold-titania nanoparticles are obtained. In the second method, a microfluidic device is used to produce colloidal water droplets in oil. Each one of the droplets contains all the nanoparticles of the final assemblies. After water evaporation, superstructures are obtained which range from doublets to porous spherical or rod-like micro-objects. These assemblies can be doped with magnetite nanoparticles and then easily manipulated with a hand magnet. The superstructures possess the catalytic activity endowed by the single nanoparticles and have the advantage of being much easier to manipulate than nanoparticles. To show these characteristics, the assemblies are used as catalysts in addition reactions of aromatic amines and thiophenols in a microfluidic environment. Furthermore, magnetic porous assemblies are functionalized with an enzyme that catalyzes the deposition of a fluorescent dye through the reduction of hydrogen peroxide. The approaches presented here use nanoparticles whose surfaces were pre-activated with a gel-layer of silica or titania. During a heat treatment of the superstructures at moderate temperatures, the gel solidifies, which results in mechanically very stable assemblies, in which the single nanoparticles are linked together via metal oxide bridges.

EPFL2012

Nanoscale superparamagnetic composite particles for biomedical applications

Mathieu Chastellain

The present thesis report deals about the material scientists contribution to the interdisciplinary European project "MAGNANOMED" involving people having very different backgrounds (physicist, chemists, biochemists, veterinary surgeons, ...). The work carried out was aimed at the development of iron oxide based nanoscale superparamagnetic composite particles for biomedical applications. Particles showing a superparamagnetic behaviour are of particular interest as they are sensitive to magnetic fields without retaining magnetisation after removal of the latter. Not only superparamagnetic particles can be guided, but they also exhibit heating properties when submitted to appropriate alternating magnetic fields. These characteristics make them promising for targeted applications where they could act as careers as well as activators. The local temperature increase can be used for confined control release of linked entities or to modify specific cells activities in a well defined area. Moreover iron oxide nanoparticles can be used for magnetic resonance imaging enhancement. No single sample could meet the requirements imposed by every application mentioned above, so the chosen strategy was first to synthesize and thoroughly characterize iron oxide nanoparticles. In a second step, the particles would serve as primary building blocks for higher order composite structures or "beads" (with one or more iron oxide cores) to be formed according to the specific needs of every particular application. The surface tailoring, so that to ensure the desired properties in physiological media and allow further functionalisation, consisted in an important part of the work. Despite the many works carried out in the field over the past decades, the needs for well controlled biocompatible superparamagnetic beads are not only important but also growing. A focus was made on three specific applications: hyperthermia (controlled heating in a well defined body area by means of an external alternating magnetic field), drug delivery (magnetic targeted drug release) and DNA purification (magnetically driven separation in vitro). A supplementary application called ferrofluid actuated micro pump is also described as it turned out that a synthesis side product could be judiciously used in this field. The achievements realized allowed to define a reproducible and versatile synthesis route, which fulfils the above mentioned criteria as summarised in the following. Iron oxide particles, which physical properties could be well controlled, were shown to generate heat when submitted to an external magnetic field suitable for medical applications. The measured power dissipated could be successfully related to the particles and field characteristics using a theoretical approach and the tremendous influence of particles size distribution was highlighted. Polyvinyl alcohol coated iron oxide particles were produced for drug delivery. Biocompatibility was asserted based on both in vitro and in vivo experiments. The particles bio-distribution could be influenced by means of a constant magnetic field (magnet) and depending on the coating nature (presence of functional groups), the cellular uptake could be controlled. Silica beads with a homogeneous iron oxide particles space distribution were synthesised in view of DNA separation using a novel approach. The bead size could be adjusted in the 20 nanometres up to several microns range. Preliminary classical plasmid automated purification experiments revealed a competitive separation yield. These results are promising in view of the final targeted application in currently developed quicker automated processes. A highly concentrated iron oxide suspension (ferrofluid) showing suitable colloidal stability was successfully applied in micropumps actuated by means of a magnetically induced ferrofluid motion. The obtained pumping characteristics such as backpressure and flow rate were better then described in literature for similar devices using water based ferrofluids. AFM 3D-view of iron oxide particles coated with polyvinyl alcohol, average height 9 nm (left) and Stonehenge monument in Britain, heaviest stone 50 tons (right). "In its day, the construction of Stonehenge was an impressive engineering feat, requiring commitment, time and vast amounts of manual labour" [http://www.britannia.com/ history/h7.html] (see appendix 12.6). Nowadays, this remark still holds for Nano-stonehenge synthesis ...

EPFL2004

Anomaly induced effects in a magnetic field

Alexey Boyarsky, Oleg Ruchayskiy

We consider a modification of electrodynamics by an additional light massive vector field, interacting with the photon via Chern-Simons-like coupling. This theory predicts observable effects for the experiments studying the propagation of light in an external magnetic field, very similar to those, predicted by theories of axion and axion-like particles. We discuss a possible microscopic origin of this theory from a theory with non-trivial gauge anomaly cancellation between massive and light particles (including, for example, millicharged fermions). Due to the conservation of the gauge current, the production of the new vector field is suppressed at high energies. As a result, this theory can avoid both stellar bounds (which exist for axions) and the bounds from CMB considered recently, allowing for positive results in experiments like ALPS, LIPPS, OSQAR, PVLAS-2, BMV, Q&A, etc. (C) 2007 Elsevier B.V. All rights reserved.